Strokes and Seizures:
what we knowKuei-Cheng Lim, MD PhD
3rd Annual Neuro Rehab SymposiumMarch 7, 2015
None
Disclosure
Cynthia V Anderson is a 74 year old post-menopausal woman with atrial fibrillation on anticoagulation but stopped warfarin 4 days ago due to elevated INR with mild cognitive impairment and diabetes
She present to ED after waking up with right hemiparesis involving face and arm more than leg. She is aphasic.
Admitted for stroke evaluation. Six hours into hospitalization she had a convulsive seizure and returned to baseline after 2 hours post-ictal state.
What is her risk of another seizure? What AED would you recommend? How long would you keep AED going? Does seizure affect her ability to participate in rehabilitation?
Case to ponder
Seizures and Epilepsy are not the same◦ Seizure is the event and epilepsy is the disease◦ Conceptual
Epileptic Seizure◦ Transient occurrence of signs/symptoms due to
abnormal excessive or synchronous neuronal activity in the brain
Epilepsy◦ A disease characterized by an enduring
predisposition to generate epileptic seizures and by the neurobiological, cognitive, psychological and social consequences of this condition
Defining Epilepsy
ILAE website – www.ilae.org/Visitors/Definition-2014-Perspective.cfm
At least 2 unprovoked (or reflex) seizures occurring more than 24 hours apart
One unprovoked seizure and a probability of further seizures similar to the general recurrence risk (at least 60%) after 2 unprovoked seizures, occurring over the next 10 years
Diagnosis of an epilepsy syndrome
Epilepsy is considered to be resolved for individuals who had age-dependent epilepsy syndrome but are now past the applicable age or those who have remained seizure-free for at least 10 years; with no seizure medications for the last 5 years
Operational (Practical) Clinical Definition of Epilepsy
Fisher RS et al. A practical clinical definition of epilepsy, Epilepsia 2014; 55:475-482
Age related diagnosis of epilepsy
Hauser WA et al. Mayo Clin Proc 1996: 71; 576-86.Kim DW et al. Epilepsia 2014: 55; 67-75.
Head Trauma
16%
Cerebrovascular 16%
Infection 15%Brain Tumor 8%
Metabolic 9%
Toxic 6%
Withdrawal 14%
Other 10%
Encephalopathy 5% Eclasmpsia 2%
Causes of Acute Symptomatic Seizures
Modified from Hauser WA. “Ch. 8. Epidemiology of Acute Symptomatic Seizures.” in The Epilepsies; A comprehensive textbook. Ed. Engel and Pedley.
IdiopathicCryptogenic
62.4%, Stroke 9.3%
Trauma 8.8%
Tumor 2.7%Infection 2.2%,
Alcohol 5.8%
Neuro-degenera-tive 4.0% MR/CP 3.5%, Other 1.3%
Etiology of Epilepsy
Modified from Banerjee PN and Hauser WA. “Ch. 5. Incidence and Prevalence” in The Epilepsies; A comprehensive textbook. Ed. Engel and Pedley.
Cerebrovascular disease is a common cause of secondary epilepsy◦ Especially in the elderly >60 years old population◦ Accounts for about a third of epilepsy pts
Post-stroke seizures occur in 4-14% of strokes (some ranges from 5-20%)
Do early onset seizures develop into epilepsy?◦ Risk of recurrent seizures varies with the definition of early
versus late onset seizures◦ Early seizures is 8-16 times more likely to have late onset
seizures than those without early seizures◦ About one-third of early onset seizures have recurrent seizures
Late onset seizures increase the risk of epilepsy◦ About 50-90% of late onset seizures have recurrent seizures
General overview of seizures and strokes
Silverman et al. Arch Neurol. 2002: 59; 195-202, Burneo et al Eur J Neurol 2010: 17; 52-58, Arboix A, et al. Stroke 1997: 28; 1590-4Camilo V and Goldstein LB. Stroke 2004: 35; 1769-75
0.2-0.8% of all strokes complicated by status epilepticus◦ About 10% of early onset seizures are in status◦ About 50-75% status cases are nonconvulsive◦ Have higher functional disability and mortality
Risk of seizures increases with cortical location, ICH/SAH
Mortality and morbidity is higher in stroke patients with seizures◦ Studies show that seizures increase risk of mortality
by 2 to 3 times
General overview of seizures and strokes
Silverman et al. Arch Neurol. 2002: 59; 195-202, Burneo et al Eur J Neurol 2010: 17; 52-58, Arboix A, et al. Stroke 1997: 28; 1590-4Camilo V and Goldstein LB. Stroke 2004: 35; 1769-75
Community stroke register of a population of 105,000 residents 2-6.5 years of follow-up 1981-1986 with follow-up to 1988 675 patients with 52 pts with one or more post stroke seizure Onset seizure defined as <24 hours Estimated 5 year risk of post-stroke seizure 11.5% (5-18% 95 CI)
Oxfordshire Community Stroke Project
Burn J et al. BMJ 1997: 315; 1582-7
Onset Post-stroke (%)
Total 675 14 5 36%
IS 545 10 4 40%
ICH 66 2 1 50%
SAH 33 2 0 0%
Unknown 31 0 0
Occurrence of post-stroke seizure after onset seizure
Burn J et al. BMJ 1997: 315; 1582-7
Any seizures Single Recurrent
Total 48 23 25 52%
IS 35 17 18 51%
ICH 7 3 4 57%
SAH 6 3 3 50%
Unknown 0 0 0
Post-stroke seizures > 24 hrs
Burn J et al. BMJ 1997: 315; 1582-7
Cortical / Lobar strokes are more likely to have seizures
Burn J et al. BMJ 1997: 315; 1582-7
No sz / No pt %
All strokes 37/904
4.10% OR
deep infarct
2/356 0.60%
1 (Ref)
lobar infarct
20/341 5.90%
11
deep ICH 4/101 4% 8
lobar ICH 7/49 14% 25.3
SAH 4/50 8% 13.2
Labovitz DL et al. Neurology 2001: 57; 200-6
1897 patients with IS/ICH stroke excluding brainstem strokes, AVMs, SAH, TIAs
168 / 1897 pts (8.9%) had a seizure◦ Ischemic stroke 140 / 1632 (8.6%)
Early onset 78pts Late onset 62pts 34 pts had recurrent seizures
◦ Hemorrhagic 28 / 265 (10.6%) Early onset 21 pts Late onset 7 pts
Patient with ischemic strokes and seizures had a worse prognosis, 30-d mortality 25% vs 7%
Seizures were more likely with cortical location of the stroke◦ HR 2.09 (1.19 - 3.68) for a seizure ◦ HR 2.13 (0.60 - 7.53) for recurrent seizures
Late onset seizures have a HR of 12 for recurrent seizures
Seizure after Stroke Study Group
Bladin CF et al. Arch Neurol 2000: 57; 1617-22.
Risk of first seizure is greatest in the first 1-2 years
Arntz R et al., PLoS One 2013;8: e55498
Type # patients n seizures Incidence%
Cumulative Risk%
Total 697 79 11.3 14
IS 425 61 14.4 16
ICH 66 11 16.7 31
TIA 206 7 3.4 5
Risk of seizures in young stroke patients (FUTURE study)
Arntz R et al., PLoS One 2013;8: e55498
Early seizure (n=25) Late seizures (n-54)
Total Single Multiple Total Single Multiple
IS 20 14 (70%)
6 (30%)
41 19 (46%)
22 (53%)
ICH 4 3 (75%)
1 (25%)
7 1(14%)
6(86%)
TIA 1 1 0 6 3 3
Late onset seizures are more likely to Recur
Arntz R et al., PLoS One 2013;8: e55498
Are the underlying causes of acute and late seizures different?◦ Focal irritability◦ Network irritability
Where is the line between early and late onset seizures?◦ Cellular / Neuronal Death◦ Gliosis◦ Blood brain barrier
What is the natural history of acute symptomatic and remote symptomatic seizures?
Treatment of Early versus Late Onset Seizures
Rochester Epidemiology Project◦ Rochester, Minnesota◦ Limited population
Records-linkage system 1955-1984◦ All medical records are linked between medical
facilities in Southeastern Minnesota◦ Retrospective
Select patients first time seizures ◦ Classify as acute symptomatic versus remote
symptomatic◦ Assess for 30 day and 10 years mortality◦ Assess for etiology of seizures
Mortality of symptomatic seizures study
Hesdorffer DC et al. Epilepsia. 2009: 50; 1102-8
Acute RemoteTotal N 262 148
N, subsequent seizures 34 72
5 yr, Risk of subsequent seizure 19% (14-25%) 65% (55-75%)
Stroke 33% (21-50%) 72% (60-82%)TBI 13% (7-25%) 47% (30-66%)
Infection 17% (10-28%) 64% (21-99%)
Risk of Recurrent Seizures
Hesdorffer DC et al. Epilepsia. 2009: 50; 1102-8
Probability of Recurrent SeizuresGreater with Remote Symptomatic
Hesdorffer DC et al. Epilepsia. 2009: 50; 1102-8
Acute Remote
Mortality, 30 days
56/262 (21.4%)
5/148 (3.4%)
Stroke 42% (32-53%) 5% (2-11%)
TBI 11% (6-20%) None
Infection 10% (5-19%) None
30 day Mortality is greater with Acute Symptomatic Seizures
Hesdorffer DC et al. Epilepsia. 2009: 50; 1102-8Szalflarski JP et al. Epilepsia 2008: 49; 974-981
Caveat – Acute seizures may not be an INDEPENDENT risk factor for mortality but is associated with hemorrhagic strokes and larger infarct size and disability.
Acute stroke is the 3rd most common cause of SE (~20-36% of all SE cases)
8% of all post-stroke seizures present in SE 10-20% of early onset seizures are in SE Subclinical seizures are missed unless there is
continuous EEG monitoring◦ Subclinical/nonconvulsive seizures are 4 times more
likely to occur than convulsive seizures.
Patients in SE are at twice the risk of mortality
Status Epilepticus in Stroke
Varelas PN and Hacein-Bey L. “Stroke and Critical Care Seizures” in Current Clinical Neurology: Seizures in Critical Care:.” Ed. PN Varels. Chapter 2, pg 21-82.Knaker et al. Epilepsia. 2006: 47; 2020-6.
Causes of status epilepticus
DeLorenzo RJ et al. Neurology 1995: 46; 1029-35.
232 patients with EEG in first 24hrs then followed up for 1 week 15 patients had seizures in first 24hrs (6.5%) 10% of EEGs had epileptiform discharges 6% had periodic lateralized epileptiform discharges (PLEDs)
◦ 71.4% evolved to status epilepticus
195/232 had diffuse or focal slowing only◦ No seizures
23/232 had epileptiform discharges◦ 3/23 had seizures
14/232 had PLEDs◦ 10 were in status epilepticus (mostly convulsive)◦ 2 had focal seizures◦ 3/14 died compared to 30/218 without PLEDs
EEG and Strokes
Mecorelli O et al Cerebrovasc Dis 2011; 31: 191-8
At least 2 unprovoked (or reflex) seizures occurring more than 24 hours apart
One unprovoked seizure and a probability of further seizures similar to the general recurrence risk (at least 60%) after 2 unprovoked seizures, occurring over the next 10 years
Diagnosis of an epilepsy syndrome
Epilepsy is considered to be resolved for individuals who had age-dependent epilepsy syndrome but are now past the applicable age or those who have remained seizure-free for at least 10 years; with no seizure medications for the last 5 years
Operational (Practical) Clinical Definition of Epilepsy
Fisher RS et al. A practical clinical definition of epilepsy, Epilepsia 2014; 55:475-482
The risk of seizure recurrent Risk of mortality Underlying cause of seizure
◦ Is it self-limiting? Medication interactions Co-morbidities of the patient Risk of adverse events
Before starting treatment consider:
Newer generation medications are preferred and are likely better tolerated◦ Lamotrigine and gabapentin are better tolerated than carbamazepine
Older generation medications may interact with oral anticoagulation or anti-thrombotic medications
CYP3A4 induction/inhibition◦ Phenytoin◦ Carbamazepine, oxcarbazepine◦ Phenobarbital◦ Valproate
Electrolyte disturbances◦ Topiramate, zonisamide (carbonic anhydrase activity)◦ Oxcarbazepine (hyponatremia)
Medication interactions
Dementia/sundowning/psychosis◦ Levetiracetam
Multiple drug rashes◦ Lamotrigine, phenytoin, carbamazepine (HLA-B* 1502), zonisamide
Woman of child bearing age◦ Valproate, carbamazepine, benzodiazepine, phenytoin,
phenobarbital
Anemia◦ Felbamate, valproate, carbamazepine
Kidney disease◦ Topiramate, zonisamide
AEDs to avoid based onPatient characteristics
Top Related